Time course of anti-inflammatory effect of low-dose radiotherapy: correlation with TGF-beta(1) expression

Radiother Oncol. 2008 Mar;86(3):399-406. doi: 10.1016/j.radonc.2007.10.032. Epub 2007 Nov 26.

Abstract

Background and purpose: Low-dose radiotherapy (LD-RT) has a potent anti-inflammatory effect, and transforming growth factor (TGF)-beta(1) is a potential mediator of this effect. The objectives of this study were to characterize the in vivo effects of LD-RT on leukocyte recruitment over time, and its relationship with TGF-beta(1) production.

Materials and methods: Mice were submitted to abdominal irradiation with a dose of 0.3 Gy, or to sham radiation and studied 5, 24, 48 or 72 h after irradiation. Four hours before the study a proinflammatory stimulus consisting of LPS or placebo was administered. Leukocyte-endothelial cell interactions in intestinal venules were assessed using intravital microscopy. Circulating levels and intestinal tissue production of TGF-beta(1) were determined.

Results: Compared to non-irradiated LPS-challenged group, the number of adherent leukocytes was significantly reduced 5, 24 and 48 h, but not 72 h after irradiation in LPS-challenged mice. Rolling leukocytes were significantly decreased at all time points analyzed. Plasma TGF-beta(1) levels were increased 5 and 24h after irradiation. Increased intestinal production during this period was corroborated by in vitro culture experiments.

Conclusions: LD-RT has a sustained inhibitory effect on leukocyte recruitment for 48 h, which is initially associated with an increase in TGF-beta(1) intestinal production.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / radiation effects
  • Cell Communication
  • Endothelial Cells / radiation effects
  • Leukocyte Count
  • Leukocyte Rolling / radiation effects
  • Leukocytes / radiation effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Radiotherapy Dosage
  • Time Factors
  • Transforming Growth Factor beta1 / biosynthesis*
  • Transforming Growth Factor beta1 / blood
  • Up-Regulation

Substances

  • Transforming Growth Factor beta1